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Background: Utilizing information technology (IT) systems, for example in form of computerized cognitive screening or exergame-based (also called active videogames) training, has gained growing interest for supporting healthy aging and to detect, prevent and treat neurocognitive disorders (NCD). To ameliorate the effectiveness of exergaming, the neurobiological mechanisms as well as the most effective components for exergame-based training remain to be established. At the same time, it is important to account for the end-users’ capabilities, preferences, and therapeutic needs during the design and development process to foster the usability and acceptance of the resulting program in clinical practice. This will positively influence adherence to the resulting exergame-based training program, which, in turn, favors more distinct training-related neurobiological effects. Objectives and Methods: This methodological paper describes the design and development process of novel exergame-based training concepts guided by a recently proposed methodological framework: The ‘Multidisciplinary Iterative Design of Exergames (MIDE): A Framework for Supporting the Design, Development, and Evaluation of Exergames for Health’ ( Li et al., 2020 ). Case Study: A step-by-step application of the MIDE-framework as a specific guidance in an ongoing project aiming to design, develop, and evaluate an exergame-based training concept with the aim to halt and/or reduce cognitive decline and improve quality of life in older adults with mild neurocognitive disorder (mNCD) is illustrated. Discussion and Conclusion: The development of novel exergame-based training concepts is greatly facilitated when it is based on a theoretical framework (e.g., the MIDE-framework). Applying this framework resulted in a structured, iterative, and evidence-based approach that led to the identification of multiple key requirements for the exergame design as well as the training components that otherwise may have been overlooked or neglected. This is expected to foster the usability and acceptance of the resulting exergame intervention in “real life” settings. Therefore, it is strongly recommended to implement a theoretical framework (e.g., the MIDE-framework) for future research projects in line with well-known checklists to improve completeness of reporting and replicability when serious games for motor-cognitive rehabilitation purposes are to be developed.

Background Early detection of cognitive impairment is among the top research priorities aimed at reducing the global burden of dementia. Currently used screening tools have high sensitivity but lack specificity at their original cut-off, while decreasing the cut-off was repeatedly shown to improve specificity, but at the cost of lower sensitivity. In 2012, a new screening tool was introduced that aims to overcome these limitations – the Quick mild cognitive impairment screen (Qmci). The original English Qmci has been rigorously validated and demonstrated high diagnostic accuracy with both good sensitivity and specificity. We aimed to determine the optimal cut-off value for the German Qmci, and evaluate its diagnostic accuracy, reliability (internal consistency) and construct validity. Methods We retrospectively analyzed data from healthy older adults (HOA; n  = 43) and individuals who have a clinical diagnosis of ‘mild neurocognitive disorder’ (mNCD; n  = 37) with a biomarker supported characterization of the etiology of mNCD of three studies of the ‘Brain-IT’ project. Using Youden’s Index, we calculated the optimal cut-off score to distinguish between HOA and mNCD. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic accuracy based on the area under the curve (AUC). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Reliability (internal consistency) was analyzed by calculating Cronbach’s α. Construct validity was assessed by analyzing convergent validity between Qmci-G subdomain scores and reference assessments measuring the same neurocognitive domain. Results The optimal cut-off score for the Qmci-G was ≤ 67 (AUC = 0.96). This provided a sensitivity of 91.9% and a specificity of 90.7%. The PPV and NPV were 89.5% and 92.9%, respectively. Cronbach’s α of the Qmci-G was 0.71 (CI 95% [0.65 to 0.78]). The Qmci-G demonstrated good construct validity for subtests measuring learning and memory. Subtests that measure executive functioning and/or visuo-spatial skills showed mixed findings and/or did not correlate as strongly as expected with reference assessments. Conclusion Our findings corroborate the existing evidence of the Qmci’s good diagnostic accuracy, reliability, and construct validity. Additionally, the Qmci shows potential in resolving the limitations of commonly used screening tools, such as the Montreal Cognitive Assessment. To verify these findings for the Qmci-G, testing in clinical environments and/or primary health care and direct comparisons with standard screening tools utilized in these settings are warranted.

Analyzing and adjusting training programs to increase exercise enjoyment is crucial to achieve long-term adherence and thus also maximize health benefits. The Exergame Enjoyment Questionnaire (EEQ) is the first questionnaire specifically developed to monitor exergame enjoyment. To be used in German speaking countries, the EEQ must be translated, cross-culturally adapted, and tested on its psychometric properties. The aim of this study was to develop (i.e., translate and cross-culturally adapt) the German Version of the EEQ (EEQ-G) and investigate its psychometric properties. Psychometric properties of the EEQ-G were tested using a cross-sectional study design. Each participant performed two consecutive exergame sessions (i.e., 'preferred' and 'unpreferred' condition) in randomized order and rated the EEQ-G as well as reference questionnaires. Internal consistency of the EEQ-G was assessed by calculating Cronbach's [alpha]. Construct validity was assessed by calculating Spearman's rank correlation coefficients (r.sub.s) between the scores of the EEQ-G and reference questionnaires. Responsiveness was analyzed by performing a Wilcoxon signed-rank test between the median EEQ-G scores of the two conditions. Fourty-three healthy older adults (HOA; mean age = 69.4 ± 4.9 years; 53.5% females) were included. Cronbach's [alpha] of the EEQ-G was 0.80. The r.sub.s values between the EEQ-G and reference questionnaire scores for intrinsic motivation, game enjoyment, physical activity enjoyment, and external motivation were 0.198 (p = 0.101), 0.684 (p < 0.001), 0.277 (p = 0.036), and 0.186 (p = 0.233), respectively. The EEQ-G was rated higher in the 'preferred' than the 'unpreferred' condition (p < 0.001, r = 0.756). The EEQ-G has high internal consistency and is responsive to changes in exergame enjoyment. The highly skewed data with ceiling effects in some of the reference questionnaires deem the construct validity of the EEQ-G to be inconclusive and thus in need of further evaluation.

BACKGROUND: Exergames provide a promising new approach to implement simultaneous motor-cognitive training, which may support preventing the decline in cognitive functioning in older adults who have mild neurocognitive disorder (mNCD). OBJECTIVES: To evaluate feasibility, system usability, and acceptance of ‘Brain-IT’ - a newly developed training concept combining exergame-based motor-cognitive training and heart rate variability (HRV) guided resonance breathing for the secondary prevention of mNCD. METHODS: A pilot randomized controlled trial (RCT) with an allocation ratio of 2 : 1 (i.e., intervention : control) was conducted. The control group proceeded with usual care. The intervention group performed a twelve-week training according to the ‘Brain-IT’ training concept implemented with the ‘Senso Flex’ (Dividat AG) exergaming system in addition to usual care. Feasibility and usability outcomes were analyzed using descriptive statistics. User acceptance was analyzed qualitatively and using Friedman analysis of variance (ANOVA) as well as Wilcoxon signed-rank tests. RESULTS: Eighteen participants (77.3 ± 9.8 years; 44.4 % females) were included. On average, we recruited 2.2 participants per month and 35.3 % of the individuals contacted were included. The intervention group had an attrition rate of 20 % and mean adherence and compliance rates of 85.0 % and 84.1 %, respectively. Mean system usability score, measured with the system usability scale, was 71.7. High levels of exergame enjoyment, an increase in exergame enjoyment and an internalization of training motivation with large effect sizes (p = 0.03, r = 0.75 and p = 0.03, r = 0.74, respectively), as well as acceptable perceived usefulness were observed. Preliminary data on the effects of the ‘Brain-IT’ training is promising. CONCLUSION: Feasibility and usability of the ‘Brain-IT’ training are acceptable. However, frequent occurrence of technical problems and difficulties in using the exergame training system were identified as barriers for performing the ‘Brain-IT’ training. To optimize feasibility, either improvements or alternative solutions are required in the hardware and software of the exergame used to implement the ‘Brain-IT’ training. The ‘Brain-IT’ training itself was well accepted by older adults who have mNCD. Therefore, the effectiveness of the ‘Brain-IT’ training concept should be investigated in future studies. TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04996654

Analyzing and adjusting training programs to increase exercise enjoyment is crucial to achieve long-term adherence and thus also maximize health benefits. The Exergame Enjoyment Questionnaire (EEQ) is the first questionnaire specifically developed to monitor exergame enjoyment. To be used in German speaking countries, the EEQ must be translated, cross-culturally adapted, and tested on its psychometric properties. The aim of this study was to develop (i.e., translate and cross-culturally adapt) the German Version of the EEQ (EEQ-G) and investigate its psychometric properties. Psychometric properties of the EEQ-G were tested using a cross-sectional study design. Each participant performed two consecutive exergame sessions (i.e., 'preferred' and 'unpreferred' condition) in randomized order and rated the EEQ-G as well as reference questionnaires. Internal consistency of the EEQ-G was assessed by calculating Cronbach's α. Construct validity was assessed by calculating Spearman's rank correlation coefficients (rs) between the scores of the EEQ-G and reference questionnaires. Responsiveness was analyzed by performing a Wilcoxon signed-rank test between the median EEQ-G scores of the two conditions. Fourty-three healthy older adults (HOA; mean age = 69.4 ± 4.9 years; 53.5% females) were included. Cronbach's α of the EEQ-G was 0.80. The rs values between the EEQ-G and reference questionnaire scores for intrinsic motivation, game enjoyment, physical activity enjoyment, and external motivation were 0.198 (p = 0.101), 0.684 (p < 0.001), 0.277 (p = 0.036), and 0.186 (p = 0.233), respectively. The EEQ-G was rated higher in the 'preferred' than the 'unpreferred' condition (p < 0.001, r = 0.756). The EEQ-G has high internal consistency and is responsive to changes in exergame enjoyment. The highly skewed data with ceiling effects in some of the reference questionnaires deem the construct validity of the EEQ-G to be inconclusive and thus in need of further evaluation.

Exergames have attracted growing interest in the prevention and treatment of neurocognitive disorders. The most effective exergame and training components (ie, exercise and training variables such as frequency, intensity, duration, or volume of training and type and content of specific exergame scenarios) however remain to be established for older adults with mild neurocognitive disorders (mNCDs). Regarding the design and development of novel exergame-based training concepts, it seems of crucial importance to explicitly include the intended users' perspective by adopting an interactive and participatory design that includes end users throughout different iterative cycles of development. This study aimed to determine the capabilities, treatment preferences, and motivators for the training of older adults with mNCD and the perspectives of individuals on training goals and settings and requirements for exergame and training components. A qualitative study including expert focus groups and individual semistructured in-depth patient interviews was conducted. Data were transcribed to a written format to perform qualitative content analysis using QCAmap software. In total, 10 experts and health care professionals (80% females) and 8 older adults with mNCD (38% females; mean age 82.4, SD 6.2 years) were recruited until data saturation was observed. The psychosocial consequences of patients' self-perceived cognitive deterioration might be more burdensome than the cognitive changes themselves. Older adults with mNCD prefer integrative forms of training (such as exergaming) and are primarily motivated by enjoyment or fun in exercising and the effectiveness of the training. Putting the synthesized perspectives of training goals, settings, and requirements for exergames and training components into context, our considerations point to opportunities for improvement in research and rehabilitation, either by adapting existing exergames to patients with mNCDs or by developing novel exergames and exergame-based training concepts specifically tailored to meet patient requirements and needs.

Mild neurocognitive disorder (mNCD) is recognized as an early stage of dementia and is gaining attention as a significant healthcare problem due to current demographic changes and increasing numbers of patients. Timely detection of mNCD provides an opportunity for early interventions that can potentially slow down or prevent cognitive decline. Heart rate variability (HRV) may be a promising measure, as it has been shown to be sensitive to cognitive impairment. However, there is currently no evidence regarding the diagnostic accuracy of HRV measurements in the context of the mNCD population. This study aimed to evaluate the diagnostic accuracy of vagally-mediated HRV (vm-HRV) as a screening tool for mNCD and to investigate the relationship between vm-HRV with executive functioning and depression in older adults who have mNCD. We retrospectively analyzed data from healthy older adults (HOA) and individuals with a clinical diagnosis of mNCD with a biomarker-supported characterization of the etiology of mNCD. Diagnostic accuracy was evaluated using receiver operating characteristic curve analysis based on the area under the curve. Sensitivity and specificity were calculated based on the optimal threshold provided by Youden's Index. Multiple linear regression analyses were conducted to investigate the relationship between vm-HRV and executive functioning and depression. This analysis included 42 HOA and 29 individuals with mNCD. The relative power of high frequency was found to be increased in individuals with mNCD. The greatest AUC calculated was 0.68 (with 95% CI: 0.56, 0.81) for the relative power of high frequency. AUCs for other vm-HRV parameters were between 0.53 and 0.61. No consistent correlations were found between vm-HRV and executive functioning or depression. It appears that vm-HRV parameters alone are insufficient to reliably distinguish between HOA and older adults with mNCD. Additionally, the relationship between vm-HRV and executive functioning remains unclear and requires further investigation. Prospective studies that encompass a broad range of neurocognitive disorders, HRV measurements, neuroimaging, and multimodal approaches that consider a variety of functional domains affected in mNCD are warranted to further investigate the potential of vm-HRV as part of a multimodal screening tool for mNCD. These multimodal measures have the potential to improve the early detection of mNCD in the future.

Background Vagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training in general. This study evaluated the test-retest reliability of vm-HRV during exergaming in healthy older adults (HOA) and its validity to monitor ITL. Methods A within-subjects (repeated-measures) randomized study was conducted that included baseline assessments and 4 measurement sessions. Participants played 5 exergames at 3 standardized levels of external task demands (i.e., “easy”, “challenging”, and “excessive”) in random order for 90 s. Test-retest reliability was assessed on the basis of repeated-measures analyses of variance (ANOVA), intraclass correlation coefficients (ICC 3,1 ), standard errors of measurement (SEM), and smallest detectable differences (SDD). Validity was determined by examining the effect of game level on vm-HRV in the ANOVA. Results Fourty-three HOA (67.0 ± 7.0 years; 58.1% females (25 females, 18 males); body mass index = 23.7 ± 3.0 kg·m −2 ) were included. Mean R-R time intervals (mRR) and parasympathetic nervous system tone index (PNS-Index) exhibited mostly good to excellent relative test-retest reliability with no systematic error. Mean SEM% and SDD% were 36.4% and 100.7% for mRR, and 44.6% and 123.7% for PNS-Index, respectively. Significant differences in mRR and PNS-Index were observed between standardized levels of external task demands, with mostly large effect sizes (mean r  = 0.847). These results persisted irrespective of the type of neurocognitive domain trained and when only motoric and cognitive demands were manipulated while physical intensity was kept constant. The remaining vm-HRV parameters showed inconsistent or poor reliability and validity. Conclusion Only mRR and PNS-Index demonstrated reliable measurement and served as valid biomarkers for ITL during exergaming at a group level. Nonetheless, the presence of large SEMs hampers the detection of individual changes over time and suggests insufficient precision of these measurements at the individual level. Future research should further investigate the reliability and validity of vm-HRV with a specific focus on comparing different measurement methodologies and exercise conditions, particularly focusing on ultra-short-term HRV measurements, and investigate the potential implications (i.e., superiority to other markers of ITL or monitoring strategies?) of using vm-HRV as a biomarker of ITL.

Introduction Exergame-based training is emerging as the most effective exercise modality for improving cognition, yet its neural correlates remain largely unexplored. This study explored gray matter (GM) and white matter (WM) changes following the addition of ‘Brain-IT’ training to usual care in mild neurocognitive disorder (mNCD) and their associations with cognitive performance changes. Methods We included 41 participants with mNCD, randomized to either the intervention (‘Brain-IT’ training + usual care) or the control (usual care only) group. ‘Brain-IT’ is a holistic, individually tailored “exercise as medicine” program for secondary mNCD prevention delivered through serious exergames. T1-weighted and diffusion tensor imaging data were analyzed via standard neuroimaging analysis pipelines (FreeSurfer, tract-based spatial statistics) to assess GM/WM volumes in predefined regions of interest and WM integrity at the voxel-to-voxel level. Intervention-related changes were explored via analyses of covariance, focusing on effect size estimates. One-sided bivariate correlation analyses explored associations between changes in brain structure and cognitive performance. Results Complete datasets from 30 study participants (72.0 ± 8.6 years; 27% females) were available. 87% of participants had biomarker-supported characterization of mNCD etiology– mostly Alzheimer’s (62%). Significant moderate to large effects (partial eta-squared = 0.109 to 0.187) on GM/WM volumes were observed in the right and total hippocampus, thalamus, and anterior cingulate cortex in favor of ‘Brain-IT’ training. Hippocampal and thalamic changes correlated with improvements in verbal delayed recall. Protective effects on WM integrity, which correlated with cognitive improvements, were also observed, mainly around the thalamic radiation and the corpus callosum. Conclusion This is the first RCT showing that a co-designed, purpose-developed, and individually tailored exergame-based training may positively impact brain structures affected in mNCD, with potential associations suggestive of a causal link to cognitive improvements. Since hippocampal atrophy is a hallmark of Alzheimer’s disease with high prognostic value for disease progression, our observations may be a first indication of a potential disease-modifying role of ‘Brain-IT’ training. However, adequately powered and hypothesis-driven studies are needed to build on these initial exploratory findings and better understand the neurobiological effects of exergame-based training. Trial registration ClinicalTrials.gov (NCT05387057; date of registration: May 18, 2022): https://clinicaltrials.gov/ct2/show/NCT05387057 .

Exergame-based training enhances physical and cognitive performance in older adults, including those with mild neurocognitive disorder (mNCD). In-game metrics generated from user interactions with exergames enable individualized adjustments. However, there is a need to systematically investigate how well such game metrics capture true cognitive and motor-cognitive performance to provide a more robust basis for personalized training. The primary objective was to identify valid game metrics as indicators for in-game domain-specific cognitive performance during exergaming in individuals with mNCD. We also aimed to explore game metric performance changes over time during exergame-based training. Data were analyzed from individuals with mNCD who completed a 12-week home-based, exergame-based intervention following the Brain-IT training concept. A cross-sectional analysis was conducted by correlating game metrics with standardized neurocognitive reference assessments. To confirm the alternative hypothesis, we predetermined the following criteria: (1) statistically significant correlation (P≤.05; uncorrected; 1-sided) with (2) a correlation coefficient (Pearson r or Spearman ρ) of ≥0.4. Visual and curve-fitting longitudinal analyses were conducted to explore game performance changes over time. Data were available from 31 participants (mean age 76.4, SD 7.5 y; n=9, 29% female). In total, 33% (6/18) of the game metrics were identified as valid indicators for in-game cognitive performance during exergaming. In the neurocognitive domain of learning and memory, these metrics included the mean reaction time (ρ=-0.747), the number of collected items (ρ=0.691), and the precision score (r=-0.607) for the game Shopping Tour (P<.001 in all cases), as well as the point rate (P=.008; r=0.471) for the game Simon. In addition, point rate was a valid indicator for executive function (P=.006; r=0.455) and visuospatial skills (P=.02; r=0.474) for the games Targets and Gears, respectively. The exploratory longitudinal analysis revealed high interindividual variability, with a general trend of the expected typical curvilinear curves of rapid initial improvements followed by a plateau in performance. This study demonstrated that metrics reflecting the precision of responses generally performed better than metrics reflecting the speed of responses. These observations highlight the importance of selecting valid game metrics for implementation in exergame designs. Further research is needed to explore the potential of game metrics and identify factors contributing to individual variability in in-game performance and performance progression, as well as identifying and adopting strategies that facilitate individual learning success and thus promote effectiveness in improving health outcomes.